{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T12:15:41Z","timestamp":1765887341321,"version":"3.28.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2012,1,1]],"date-time":"2012-01-01T00:00:00Z","timestamp":1325376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>The purpose of this study was to demonstrate the effects of the tight junction permeation enhancer, AT1002, on the nasal absorption of molecular weight markers and low bioavailable therapeutic agents co-administered with bioadhesive polymers or zonulin antagonist.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The bioadhesive polymers, carrageenan and Na-CMC, were prepared with AT1002 to examine the permeation-enhancing effect of AT1002 on the nasal absorption of inulin, calcitonin and saquinavir after nasal administration to Sprague\u2013Dawley rats. Blood samples were collected over a 6-hour period from a jugular cannula. In addition, we determined whether AT1002 exerts a permeation-enhancing effect via activation of PAR-2 specific binding to a putative receptor of zonulin. To examine this zonulin antagonist, AT1001, was administered 30 min prior to dosing with an AT1002\/inulin solution and blood samples were collected over a 6-hour period.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key findings<\/jats:title>\n                  <jats:p>The bioadhesive polymers did not directly increase the absorption of inulin, calcitonin and saquinavir, but promoted the permeation-enhancing effect of AT1002 when delivered nasally, thereby significantly increasing the absorption of each drug. Pre-treatment with AT1001 antagonized the zonulin receptor and significantly minimized the permeation-enhancing effect of AT1002.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>These findings will assist in understanding the permeation-enhancing capability of and the receptor binding of AT1002. Further, combining AT1002 with carrageenan supports the development of the mucosal delivery of therapeutic agents that have low bioavailability even with bioadhesive agents.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1111\/j.2042-7158.2011.01381.x","type":"journal-article","created":{"date-parts":[[2011,11,21]],"date-time":"2011-11-21T14:14:42Z","timestamp":1321884882000},"page":"30-39","source":"Crossref","is-referenced-by-count":7,"title":["The influence of AT1002 on the nasal absorption of molecular weight markers and therapeutic agents when co-administered with bioadhesive polymers and an AT1002 antagonist, AT1001"],"prefix":"10.1093","volume":"64","author":[{"given":"Keon-Hyoung","family":"Song","sequence":"first","affiliation":[{"name":"Pharmacokinetics-Biopharmaceutics Laboratory, Department of Pharmaceutical Science, School of Pharmacy, University of Maryland , Baltimore, MD,","place":["USA"]},{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University , Seoul,","place":["Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie D","family":"Eddington","sequence":"additional","affiliation":[{"name":"Pharmacokinetics-Biopharmaceutics Laboratory, Department of Pharmaceutical Science, School of Pharmacy, University of Maryland , Baltimore, MD,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2012,1,1]]},"reference":[{"key":"2024103013315595600_cit1","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1002\/jnr.10762","article-title":"HIV-1 Tat protein alters tight junction protein expression and distribution in cultured brain endothelial cells","volume":"74","author":"Andras","year":"2003","journal-title":"J Neurosci Res"},{"key":"2024103013315595600_cit2","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1517\/17425247.2.2.281","article-title":"Advances in nasal drug delivery through tight junction technology","volume":"2","author":"Johnson","year":"2005","journal-title":"Expert Opin Drug Deliv"},{"key":"2024103013315595600_cit3","doi-asserted-by":"crossref","first-page":"L431","DOI":"10.1152\/ajplung.90256.2008","article-title":"Endothelial EphA receptor stimulation increases lung vascular permeability","volume":"295","author":"Larson","year":"2008","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2024103013315595600_cit4","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S0939-6411(01)00172-2","article-title":"Enhancing the permeation of marker compounds and enaminone anticonvulsants across Caco-2 monolayers by modulating tight junctions using zonula occludens toxin","volume":"52","author":"Cox","year":"2001","journal-title":"Eur J Pharm Biopharm"},{"key":"2024103013315595600_cit5","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1023\/A:1020709513562","article-title":"Enhanced permeability of molecular weight markers and poorly bioavailable compounds across Caco-2 cell monolayers using the absorption enhancer, zonula occludens toxin","volume":"19","author":"Cox","year":"2002","journal-title":"Pharm Res"},{"key":"2024103013315595600_cit6","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1002\/jps.10310","article-title":"Zonula occludens toxin increases the permeability of molecular weight markers and chemotherapeutic agents across the bovine brain microvessel endothelial cells","volume":"92","author":"Karyekar","year":"2003","journal-title":"J Pharm Sci"},{"key":"2024103013315595600_cit7","doi-asserted-by":"crossref","first-page":"19160","DOI":"10.1074\/jbc.M009674200","article-title":"Zonula occludens toxin structure-function analysis. 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